tbuckley/cabot-search huggingface dataset:
The GETUG SEMITEP Trial: De-escalating Chemotherapy in Good-prognosis Seminoma Based on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Yohann Loriot, Matthieu Texier, Stéphane Culine, Aude Fléchon, Antoine Thiery-Vuillemin, Gwenaëlle Gravis, Lionel Geoffrois, Christine Chevreau, Marine Gross-Goupil, Philippe Barthelemy, Emmanuelle Bompas, Hakim Mahammedi, Brigitte Laguerre, Sophie Abadie Lacourtoisie, Carole Helissey, Sylvain Ladoire, Christine Abraham, Christophe Massard, Serena Grimaldi, Karim Fizazi
Journal: European Urology (2022)
mRNA vaccine effectiveness against hospitalisation due to severe acute respiratory infection (SARI) COVID-19 during Omicron variant predominance estimated from real-world surveillance data, Slovenia, February to March 2022
Authors: Marta Grgič Vitek, Irena Klavs, Veronika Učakar, Marjana Vrh, Maja Mrzel, Mojca Serdt, Mario Fafangel
Journal: Eurosurveillance (2022)

For the period of predominance of SARS-CoV-2 Omicron variant in Slovenia, February to March 2022, we estimated mRNA vaccine effectiveness (VE) against severe acute respiratory infection (SARI) COVID-19 using surveillance data. In the most vulnerable age group comprising individuals aged 65 years and more, VE against SARI COVID-19 was 95% (95% CI: 95-96%) for those vaccinated with three doses, in comparison to 82% (95% CI: 79-84%) for those vaccinated with two doses. Such levels of protection were maintained for at least 6 months.
RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System
Authors: Wout De Mey, Arthur Esprit, Kris Thielemans, Karine Breckpot, Lorenzo Franceschini
Journal: Clinical Cancer Research (2022)

Recent advances in the manufacturing, modification, purification, and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array of applications. The approval of two SARS-CoV-2-targeting mRNA-based vaccines has highlighted the advances of this technology. Offering rapid and straightforward manufacturing, clinical safety, and versatility, this paves the way for RNA therapeutics to expand into cancer immunotherapy. Together with ongoing trials on RNA cancer vaccination and cellular therapy, RNA therapeutics could be introduced into clinical practice, possibly stewarding future personalized approaches. In the present review, we discuss recent advances in RNA-based immuno-oncology together with an update on ongoing clinical applications and their current challenges.
A novel spinal neuron connection for heat sensation
Authors: Hongsheng Wang, Wenbing Chen, Zhaoqi Dong, Guanglin Xing, Wanpeng Cui, Lingling Yao, Wen-Jun Zou, Heath L. Robinson, Yaoyao Bian, Zhipeng Liu, Kai Zhao, Bin Luo, Nannan Gao, Hongsheng Zhang, Xiao Ren, Zheng Yu, James Meixiong, Wen-Cheng Xiong, Lin Mei
Journal: Neuron (2022)
Clinical Applications of FDG-PET Scan in Arrhythmic Myocarditis
Authors: Giovanni Peretto, Elena Busnardo, Paola Ferro, Anna Palmisano, Davide Vignale, Antonio Esposito, Giacomo De Luca, Corrado Campochiaro, Silvia Sartorelli, Monica De Gaspari, Stefania Rizzo, Lorenzo Dagna, Cristina Basso, Luigi Gianolli, Paolo Della Bella, Simone Sala
Journal: JACC. Cardiovascular imaging (2022)
Infertility—why the silence?
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2022)

The most common story of the state of reproductive health in many low- and middle-income countries is one of high rates of fertility, limited access to and low use of contraception, and high unmet need for family planning information and services. Indeed, the evidence on these issues is clear, as shown in many research articles and comments published in this journal. But there's one aspect of reproductive health that's conspicuously side-lined from global health research and policy today—infertility.
Emerging role for thymic stromal lymphopoietin–responsive regulatory T cells in colorectal cancer progression in humans and mice
Authors: Kazushige Obata-Ninomiya, Steven de Jesus Carrion, Alex Hu, Steven F. Ziegler
Journal: Science Translational Medicine (2022)

Recruitment of regulatory T cells (T regs ) to tumors is a hallmark of cancer progression. Tumor-derived factors, such as the cytokine thymic stromal lymphopoietin (TSLP), can influence T reg function in tumors. In our study, we identified a subset of T regs expressing the receptor for TSLP (TSLPR + T regs ) that were increased in colorectal tumors in humans and mice and largely absent in adjacent normal colon. This T reg subset was also found in the peripheral blood of patients with colon cancer but not in the peripheral blood of healthy control subjects. Mechanistically, we found that this T reg subset coexpressed the interleukin-33 (IL-33) receptor [suppressor of tumorigenicity 2 (ST2)] and had high programmed cell death 1 (PD-1) and cytotoxic lymphocyte–associated antigen 4 (CTLA-4) expression, regulated in part by the transcription factor Mef2c. T reg -specific deletion of TSLPR, but not ST2, was associated with a reduction in tumor number and size with concomitant increase in T H 1 cells in tumors in chemically induced mouse models of colorectal cancer. Therapeutic blockade of TSLP using TSLP-specific monoclonal antibodies effectively inhibited the progression of colorectal tumors in this mouse model. Collectively, these data suggest that TSLP controls the progression of colorectal cancer through regulation of tumor-specific T reg function and represents a potential therapeutic target that requires further investigation.
Albuterol–Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma
Authors: Alberto Papi, Bradley E. Chipps, Richard Beasley, Reynold A. Panettieri, Elliot Israel, Mark Cooper, Lynn Dunsire, Allison Jeynes-Ellis, Eva Johnsson, Robert Rees, Christy Cappelletti, Frank C. Albers
Journal: New England Journal of Medicine (2022)

As asthma symptoms worsen, patients typically rely on short-acting β2-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation.
Centering the relationship between structural racism and individual bias
Authors: Agustín Fuentes, Laurence Ralph, Dorothy E. Roberts
Journal: Behavioral and Brain Sciences (2022)

Cesario misrepresents or ignores data on real-world racist and sexist patterns and processes in an attempt to discredit the assumptions of implicit bias experimentation. His position stands in stark contradiction to substantive research across the social sciences recognizing the widespread, systematic, and structuring processes of racism and sexism. We argue for centering the relationship between structural racism and individual bias.
Sodium Glucose Cotransporter-2 Inhibition for Acute Myocardial Infarction
Authors: Jacob A. Udell, W. Schuyler Jones, Mark C. Petrie, Josephine Harrington, Stefan D. Anker, Deepak L. Bhatt, Adrian F. Hernandez, Javed Butler
Journal: Journal of the American College of Cardiology (2022)

Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality.
Pirtobrutinib inhibits wild-type and mutant Bruton’s tyrosine kinase-mediated signaling in chronic lymphocytic leukemia
Authors: Burcu Aslan, Gorkem Kismali, Lakesla R. Iles, Ganiraju C. Manyam, Mary L. Ayres, Lisa S. Chen, Mihai Gagea, Maria Teresa Sabrina Bertilaccio, William G. Wierda, Varsha Gandhi
Journal: Blood Cancer Journal (2022)

Abstract Pirtobrutinib (LOXO-305), a reversible inhibitor of Bruton’s tyrosine kinase (BTK), was designed as an alternative strategy to treat ibrutinib-resistant disease that develops due to C481 kinase domain mutations. The clinical activity of pirtobrutinib has been demonstrated in CLL, but the mechanism of action has not been investigated. We evaluated pirtobrutinib in 4 model systems: first, MEC-1, a CLL cell line overexpressing BTK WT , BTK C481S , or BTK C481R ; second, murine models driven by MEC-1 overexpressing BTK WT or BTK C481S ; third, in vitro incubations of primary CLL cells; and finally, CLL patients during pirtobrutinib therapy (NCT03740529, ClinicalTrials.gov). Pirtobrutinib inhibited BTK activation as well as downstream signaling in MEC-1 isogenic cells overexpressing BTK WT , BTK C481S , or BTK C481R . In mice, overall survival was short due to aggressive disease. Pirtobrutinib treatment for 2 weeks led to reduction of spleen and liver weight in BTK WT and BTK C481S cells, respectively. In vitro incubations of CLL cells harboring wild-type or mutant BTK had inhibition of the BCR pathway with either ibrutinib or pirtobrutinib treatment. Pirtobrutinib therapy resulted in inhibition of BTK phosphorylation and downstream signaling initially in all cases irrespective of their BTK profile, but these effects started to revert in cases with other BCR pathway mutations such as PLCG2 or PLEKHG5. Levels of CCL3 and CCL4 in plasma were marginally higher in patients with mutated BTK; however, there was a bimodal distribution. Both chemokines were decreased at early time points and mimicked BCR pathway protein changes. Collectively, these results demonstrate that pirtobrutinib is an effective BTK inhibitor for CLL harboring wild-type or mutant BTK as observed by changes in CCL3 and CCL4 biomarkers and suggest that alterations in BCR pathway signaling are the mechanism for its clinical effects. Long-term evaluation is needed for BTK gatekeeper residue variation along with pathologic kinase substitution or mutations in other proteins in the BCR pathway.
Predatory bacterial hydrogels for topical treatment of infected wounds
Authors: Yan Liu, Bo Zhuang, Bochuan Yuan, Hui Zhang, Jingfei Li, Wanmei Wang, Ruiteng Li, Lina Du, Pingtian Ding, Yiguang Jin
Journal: Acta Pharmaceutica Sinica B (2022)

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.
Correction: EVALUATION OF THE EFFECT OF GASTRIC TARGETED BIOPSY SAMPLING WITH I-SCAN OE TECHNOLOGY ON THE DIAGNOSTIC YIELD OF THE CLO TEST OF H. PYLORI INFECTION
Authors: H. Dawod
Journal: Endoscopy (2022)

Correction to: EVALUATION OF THE EFFECT OF GASTRIC TARGETED BIOPSY SAMPLING WITH I-SCAN OE TECHNOLOGY ON THE DIAGNOSTIC YIELD OF THE CLO TEST OF H. PYLORI INFECTIONEndoscopy 2022; 54(S 01): eP113DOI: 10.1055/s-0042-1744966
Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants
Authors: Jumana Samara, Shirin Moossavi, Belal Alshaikh, Van A. Ortega, Veronika Kuchařová Pettersen, Tahsin Ferdous, Suzie L. Hoops, Amuchou Soraisham, Joseph Vayalumkal, Deonne Dersch-Mills, Jeffrey S. Gerber, Sagori Mukhopadhyay, Karen Puopolo, Thomas A. Tompkins, Dan Knights, Jens Walter, Harish Amin, Marie-Claire Arrieta
Journal: Cell Host & Microbe (2022)
Diagnosis and Management of Infective Endocarditis in People Who Inject Drugs
Authors: Evin Yucel, Benjamin Bearnot, Molly L. Paras, Emily K. Zern, David M. Dudzinski, Chen-Pang Soong, Arminder S. Jassar, Kenneth Rosenfield, Jaclynne Lira, Eugene Lambert, Sarah E. Wakeman, Thoralf Sundt
Journal: Journal of the American College of Cardiology (2022)
A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions
Authors: Evan S. Dellon, Paneez Khoury, Amanda B. Muir, Chris A. Liacouras, Ekaterina Safroneeva, Dan Atkins, Margaret H. Collins, Nirmala Gonsalves, Gary W. Falk, Jonathan M. Spergel, Ikuo Hirano, Mirna Chehade, Alain M. Schoepfer, Calies Menard-Katcher, David A. Katzka, Peter A. Bonis, Albert J. Bredenoord, Bob Geng, Elizabeth T. Jensen, Robert D. Pesek, Paul Feuerstadt, Sandeep K. Gupta, Alfredo J. Lucendo, Robert M. Genta, Girish Hiremath, Emily C. McGowan, Fouad J. Moawad, Kathryn A. Peterson, Marc E. Rothenberg, Alex Straumann, Glenn T. Furuta, Seema S. Aceves
Journal: Journal of Allergy and Clinical Immunology (2022)
Severe acute hepatitis and acute liver failure of unknown origin in children: a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022
Authors: Ruben H de Kleine, Willem S Lexmond, Gustav Buescher, Ekkehard Sturm, Deidre Kelly, Ansgar W Lohse, Dominic Lenz, Marianne Hørby Jørgensen
Journal: Eurosurveillance (2022)

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3–5, 0–2 and 3–5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0–8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise.
Sex-Based Disparities in Timeliness of Trauma Care and Discharge Disposition
Authors: Martha-Conley E. Ingram, Monica Nagalla, Ying Shan, Brian J. Nasca, Arielle C. Thomas, Susheel Reddy, Karl Y. Bilimoria, Anne Stey
Journal: JAMA Surgery (2022)

Differences in time to diagnostic and therapeutic measures can contribute to disparities in outcomes. However, whether there is an association of timeliness by sex for trauma patients is unknown.
Therapeutic Implications for Intrinsic Phenotype Classification of Metastatic Castration-Resistant Prostate Cancer
Authors: Ilsa M. Coleman, Navonil DeSarkar, Colm Morrissey, Li Xin, Martine P. Roudier, Erolcan Sayar, Dapei Li, Eva Corey, Michael C. Haffner, Peter S. Nelson
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To determine whether metastatic castration–resistant prostate cancers (mCRPC) partition into molecular phenotypes corresponding to intrinsic differentiation states and ascertain whether these subtypes exhibit specific druggable features and associate with treatment outcomes. Experimental Design: We used RNAseq, digital spatial profiling, and histological assessments from metastatic biopsies and patient-derived xenografts to segregate mCRPCs into subtypes defined by the PAM50 breast cancer classification algorithm. Subtype associations with treatment responses in preclinical models and patients were determined. Results: Using the PAM50 algorithm, we partitioned 270 mCRPC tumors into LumA (42%), LumB (24%), and Basal (34%) subtypes with classification largely driven by proliferation rates and androgen receptor (AR) activity. Most neuroendocrine tumors classified as Basal. Pathways enriched in the LumA subtype include TGFß and NOTCH signaling. LumB subtype tumors were notable for elevated MYC activity. Basal subtype tumors exhibited elevated IL6-STAT3 signaling and features of adult stem cell states. In patients where multiple tumors were evaluated, the majority had concordant PAM50 subtype determination, though a subset exhibited marked inter- and intratumor heterogeneity, including divergent classifications between primary and metastatic sites. In preclinical models, LumA subtype tumors were highly responsive to androgen deprivation and docetaxel chemotherapy whereas Basal tumors were largely resistant. In clinical cohorts patients with Basal subtype tumors demonstrated a shorter time on treatment with AR signaling inhibitors and docetaxel relative to patients with luminal subtypes. Conclusions: Subtyping of mCRPC based on cell differentiation states has potential clinical utility for identifying patients with divergent expression of treatment targets and responses to systemic therapy.
Inferior cellular and humoral immunity against Omicron and Delta variants of concern compared with SARS-CoV-2 wild type in hemodialysis patients immunized with 4 SARS-CoV-2 vaccine doses
Authors: Moritz Anft, Arturo Blazquez-Navarro, Michael Frahnert, Lutz Fricke, Toni L. Meister, Toralf Roch, Ulrik Stervbo, Stephanie Pfaender, Timm H. Westhoff, Nina Babel
Journal: Kidney International (2022)
The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease
Authors: Rebekah J. Nicholson, Marie K. Norris, Annelise M. Poss, William L. Holland, Scott A. Summers
Journal: Annual Review of Nutrition (2022)

Diet influences onset, progression, and severity of several chronic diseases, including heart failure, diabetes, steatohepatitis, and a subset of cancers. The prevalence and clinical burden of these obesity-linked diseases has risen over the past two decades. These metabolic disorders are driven by ectopic lipid deposition in tissues not suited for fat storage, leading to lipotoxic disruption of cell function and survival. Sphingolipids such as ceramides are among the most deleterious and bioactive metabolites that accrue, as they participate in selective insulin resistance, dyslipidemia, oxidative stress and apoptosis. This review discusses our current understanding of biochemical pathways controlling ceramide synthesis, production and action; influences of diet on ceramide levels; application of circulating ceramides as clinical biomarkers of metabolic disease; and molecular mechanisms linking ceramides to altered metabolism and survival of cells. Development of nutritional or pharmacological strategies to lower ceramides could have therapeutic value in a wide range of prevalent diseases.
Trajectories of quality of life recovery and symptom burden after autologous hematopoietic cell transplantation in multiple myeloma
Authors: Anita D'Souza, Ruta Brazauskas, Edward A. Stadtmauer, Marcelo C. Pasquini, Parameswaran Hari, Asad Bashey, Natalie Callander, Steven Devine, Yvonne Efebera, Siddhartha Ganguly, Cristina Gasparetto, Nancy Geller, Mary M. Horowitz, John Koreth, Heather Landau, Claudio Brunstein, Philip McCarthy, Muzaffar H. Qazilbash, Sergio Giralt, Amrita Krishnan, Kathryn E. Flynn
Journal: American Journal of Hematology (2022)

Abstract Early autologous hematopoietic cell transplantation (AHCT) with post‐transplant maintenance therapy is standard of care in multiple myeloma (MM). While short‐term quality of life (QOL) deterioration after AHCT is known, the long‐term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT ( N = 758), was conducted. FACT‐BMT scores up to 4 years post‐AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as ‘none/mild’ for scores 0–2 and ‘moderate/severe’ for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1‐year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow‐up was 6 years (range, 0.4–8.5 years). FACT‐BMT scores improved between enrollment and 1‐year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1‐year, and 32% at 4 years post‐AHCT. Predictors of low symptom burden at 1‐year included low symptom burden at baseline: OR 2.7 (1.8–4.1), p &lt; 0.0001; older age: OR 2.1 (1.3–3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4–3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT‐BMT and subscale scores to population norms by 1‐year post‐transplant, though many patients continue to report moderate to severe severity in some symptoms at 1‐year and beyond.
Implications of Cross-System Use Among US Veterans With Advanced Kidney Disease in the Era of the MISSION Act
Authors: Ann M. O’Hare, Catherine R. Butler, Ryan J. Laundry, Whitney Showalter, Jeffrey Todd-Stenberg, Pam Green, Paul L. Hebert, Virginia Wang, Janelle S. Taylor, Marieke Van Eijk, Kameron L. Matthews, Susan T. Crowley, Evan Carey
Journal: JAMA Internal Medicine (2022)

Since 2014, when Congress passed the Veterans Access Choice and Accountability (Choice) Act (replaced in 2018 with the more comprehensive Maintaining Internal Systems and Strengthening Integrated Outside Networks [MISSION] Act), the Department of Veterans Affairs (VA) has been paying for US veterans to receive increasing amounts of care in the private sector (non-VA care or VA community care). However, little is known about the implications of these legislative changes for the VA system.To describe the implications for the VA system of recent increases in VA-financed non-VA care.This qualitative study was a thematic analysis of documentation in the electronic health records (EHRs) of a random sample of US veterans with advanced kidney disease between June 6, 2019, and February 5, 2021.Mentions of community care in participant EHRs.Dominant themes pertaining to VA-financed non-VA care.Among 1000 study participants, the mean (SD) age was 73.8 (11.4) years, and 957 participants (95.7%) were male. Three interrelated themes pertaining to VA-financed non-VA care emerged from qualitative analysis of documentation in cohort member EHRs: (1) VA as mothership, which describes extensive care coordination by VA staff members and clinicians to facilitate care outside the VA and the tendency of veterans and their non-VA clinicians to rely on the VA to fill gaps in this care; (2) hidden work of veterans, which describes the efforts of veterans and their family members to navigate the referral process, and to serve as intermediaries between VA and non-VA clinicians; and (3) strain on the VA system, which describes a challenging referral process and the ways in which cross-system care has stretched the traditional roles of VA staff and clinicians and interfered with VA care processes.The findings of this qualitative study describing VA-financed non-VA care for veterans with advanced kidney disease spotlight the substantial challenges of cross-system use and the strain placed on the VA system, VA staff and clinicians, and veterans and their families in recent years. These difficult-to-measure consequences of cross-system care should be considered when budgeting, evaluating, and planning the provision of VA-financed non-VA care in the private sector.